Despite wide variations in the clinical manifestations of schizophrenia, it remains difficult for clinicians to design novel treatments or predict vulnerability to negative outcomes (including medication side effects) based on signs and symptoms of the disorder. By focusing on certain clinical characteristics of schizophrenia we have designed a series of experimental medication treatments. This involves the notion that the disorder is associated with impaired cognitive performance. Hence, we have begun trials of medication that may improve cognition. Our first such trial utilized DDAVP with at least modest success. In addition we have looked for clinical manifestations potentially associated with poor outcomes. We have found that patients with schizophrenia are more assaultive than other seriously ill psychiatric patients while in the hospital and that a previous history of assaultive is associated with an increased number of hospitalizations. With regards to the major side effect of neuroleptic treatment, tardive dyskinesia (TD), we have found that depression may be associated with a more severe variant.